Every year, there are approximately 160,000 new cases of and 26,000 deaths from prostate cancer (PCa) in the United States. The majority of patients diagnosed with PCa in the United States currently opt for a radical prostatectomy procedure which involves surgical excision of the prostate gland. After a radical prostatectomy, a patient's prostate specific antigen (PSA) levels are monitored. If the PSA levels rise above a threshold of 0.2 ng/mL, the patient is determined to have biochemical recurrence (BCR). In some of these patients, the cancer metastasizes, spreading beyond the prostate. BCR occurs in approximately 20-30% of patients within five years of a radical prostatectomy, and metastasis develops in approximately 20% of patients within fifteen years of a radical prostatectomy. Of patients who experience BCR post-surgery, approximately 34% develop metastasis and approximately 70% suffer PCa specific mortality.
Computerized histomorphometric analysis of PCa hematoxylin and eosin (H&E) stained tissue images may be used to predict cancer grade, aggressiveness and risk of biochemical recurrence. Gland angularity may be strongly predictive of BCR in H&E prostate tissue images. Quantitative histomorphometry features of nuclear texture, architecture, and shape extracted from surgically resected H&E tissue images may be predictive of Gleason grade and risk of disease recurrence. For instance, nuclear roundness, alterations in nuclear structure, and morphometry acquired from H&E stained images may be useful in predicting cancer progression, outcome, and BCR. Nuclear shape and arrangement as characterized by Voronoi and Delaunay Triangulation graphs may also be predictive of BCR.
Other existing approaches to predicting BCR use QH features calculated from Feulgen stained images. The Feulgen stain binds with DNA within the nucleus of the cell and thus provides functional characterization of the cancer. The level of dye that each cell uptakes in the Feulgen stain is correlated to the amount of DNA it contains. The extent of Feulgen staining may be linked with cancer presence and aggressiveness. Some approaches use nuclear architecture and texture to characterize Feulgen stained images to predict patient outcome. Combining measurements relating to nuclear size, shape, and texture from Feulgen stained images may facilitate prediction of progression of prostate cancer. Nuclear size and shape, DNA content, and texture features relating to chromatin organization may be predictive of BCR, metastasis, and PCa specific death.
The aforementioned existing approaches focus on histomorphometric features extracted from within the tumor region to predict BCR and metastasis. However, tumor adjoining benign appearing regions may be relevant to predicting disease outcome. Nuclear morphometric features from within tumor adjacent benign (TAB) regions on surgically resected prostate specimens may be more predictive of BCR than corresponding features from within the tumor. One existing approach employs simple features related to nuclear shape to predict metastasis in PCa.
While a number of molecular assays for predicting PCa risk, BCR, progression, and metastasis have been proposed, all of these tests have tended to be tissue destructive. Additionally, these existing tests involve molecular measurements being assessed from the tumor region alone and hence may not capture a comprehensive portrait of intra-tumoral heterogeneity, and are thus sub-optimal in their predictive ability for predicting disease aggressiveness and outcome. Furthermore, apart from the deleterious side-effects of chemotherapy to the patient, in this era of spiraling healthcare costs, it must also be noted that these treatments are remarkably expensive. Consequently, there is a clinical unmet need for identifying PCa patients at elevated risk for BCR and metastasis who will receive added benefit from chemotherapy post-surgery.